Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
Mol Pharm. 2011 Jun 6;8(3):788-98. doi: 10.1021/mp100393j. Epub 2011 Apr 22.
Targeted gene delivery using nonviral vectors is a highly touted scheme to reduce the potential for toxic or immunological side effects by reducing dose. In previous reports, TAT polyplexes with DNA have shown relatively poor gene delivery. The transfection efficiency has been enhanced by condensing TAT/DNA complexes to a small particle size using calcium. To explore the targetability of these condensed TAT complexes, LABL peptide targeting intercellular cell-adhesion molecule-1 (ICAM-1) was conjugated to TAT peptide using a polyethylene glycol (PEG) spacer. PEGylation reduced the transfection efficiency of TAT, but TAT complexes targeting ICAM-1 expressing cells regained much of the lost transfection efficiency. Targeted block peptides properly formulated with calcium offer promise for gene delivery to ICAM-1 expressing cells at sites of injury or inflammation.
利用非病毒载体进行靶向基因传递是一种备受推崇的方案，通过降低剂量来减少潜在的毒性或免疫副作用。在以前的报告中，TAT 多聚物与 DNA 的结合显示出相对较差的基因传递效率。通过使用钙离子将 TAT/DNA 复合物凝聚成小颗粒大小，可以提高转染效率。为了探索这些凝聚的 TAT 复合物的靶向性，LABL 肽靶向细胞间黏附分子-1（ICAM-1）被使用聚乙二醇（PEG）间隔物连接到 TAT 肽上。PEGylation 降低了 TAT 的转染效率，但靶向表达 ICAM-1 的细胞的 TAT 复合物恢复了大部分丢失的转染效率。与钙正确配方的靶向阻断肽为在损伤或炎症部位向表达 ICAM-1 的细胞输送基因提供了希望。
